Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

• Published in: Toxicology and applied pharmacology 2012-08, Vol.262 (3), p.283-292
• Main Authors: Sebastian, Katrin, Ott, Hagen, Zwadlo-Klarwasser, Gabriele, Skazik-Voogt, Claudia, Marquardt, Yvonne, Czaja, Katharina, Merk, Hans F., Baron, Jens Malte
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Allergic diseases; AMP; Ampicillin - adverse effects; Ampicillin - pharmacology; ANIMAL CELLS; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacology; Antibacterial agents; ANTIBIOTICS; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Carboxylic Ester Hydrolases - analysis; Carcinoma, Renal Cell - chemistry; Carcinoma, Renal Cell - metabolism; Carrier Proteins - analysis; Cell Line; Cell Line, Tumor; Delayed-type-hypersensitivity; DENDRITES; Dendritic cells; Dendritic Cells - chemistry; Dendritic Cells - drug effects; DMSO; DNA-Binding Proteins - analysis; ENZYMES; GENES; Glutamate-Cysteine Ligase - analysis; Humans; Immunopathology; IN VITRO; In Vitro Techniques; Interleukin-1beta - analysis; Interleukin-8 - analysis; LACTAMS; Langerhans Cells - chemistry; Langerhans Cells - drug effects; LYMPHOKINES; Macrophages - chemistry; Macrophages - drug effects; Medical sciences; MESSENGER-RNA; METABOLIC ACTIVATION; MOLECULAR WEIGHT; MONOCYTES; Monocytes - chemistry; Monocytes - drug effects; NAD(P)H Dehydrogenase (Quinone) - analysis; Nuclear Proteins - analysis; Penicillin G - adverse effects; Penicillin G - pharmacology; Penicillin V - adverse effects; Penicillin V - pharmacology; Pharmacology. Drug treatments; POLYMERASE CHAIN REACTION; Prohapten/hapten; Real-Time Polymerase Chain Reaction; Skin allergic diseases. Stinging insect allergies; SODIUM; Sulfamethoxazole; Sulfamethoxazole - adverse effects; Sulfamethoxazole - pharmacology; SULFATES; SULFONAMIDES; SULFONIC ACIDS; THP-1; Toxicology; TRANSCRIPTION; TRANSCRIPTION FACTORS; Transcription Factors - analysis; β-Lactam antibiotics
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2012.04.038

Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.